4YWZ

Crystal structure of the extracellular receptor domain of the essential sensor kinase WalK from Staphylococcus aureus

Summary for 4YWZ

• Entry DOI: 10.2210/pdb4ywz/pdb
• Descriptor: Sensor protein kinase WalK (2 entities in total)
• Functional Keywords: extracellular receptor, kinase, essential, staphylococcus aureus, transferase
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 34802.72

Authors

Ji, Q.,Wawrzak, Z.,He, C. (deposition date: 2015-03-21, release date: 2016-03-30, Last modification date: 2024-10-30)

Primary citation

Ji, Q.,Chen, P.J.,Qin, G.,Deng, X.,Hao, Z.,Wawrzak, Z.,Yeo, W.S.,Quang, J.W.,Cho, H.,Luo, G.Z.,Weng, X.,You, Q.,Luan, C.H.,Yang, X.,Bae, T.,Yu, K.,Jiang, H.,He, C.
Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus.
Nat Commun, 7:11000-11000, 2016

PubMed Abstract: Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase 'WalK' (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resulted in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. The molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.

PubMed: 26987594
DOI: 10.1038/ncomms11000

Experimental method

X-RAY DIFFRACTION (1.7 Å)